Analysis of DNA damage and repair from low doses of radiation and drugs in mammalian cells is essential for an understanding, on a molecular level, of the therapeutic and lethal effects of such agents. We propose to continue our studies in this area using the recently developed hydrodynamic technique of viscoelastometry. Our initial experiments have established several unique properties of this method for the detection of DNA damage and repair. As this approach does not require radioactive labeling of DNA nor large numbers of cells, it is well suited to the analysis of differential effects in normal versus tumor cells in non-proliferating systems such as the CNS. Initially efforts will focus on the characterization of the viscoelastic response of neutral mammalian cell lysates and detection of double-strand breaks. Then we will analyze DNA damage and repair from radiation and certain drugs, such the nitrosoureas, spirohydantoin mustard, ellipticine, cis-diamminedichloride platinum and difluoromethylornithine. These compounds will be studied first as single agents and then in particular combination and in multimodality modes. In the long term, results of this research should lead to improved therapy of human cancer.